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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/219751
D816V KIT mutation induces mitochondrial morphologic and functional changes through BNIP3 downregulation in human myeloid cell lines ROSA and TF-1
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The KIT receptor is a transmembrane protein found on the surface of many different cell types. Mutant forms of KIT are drivers of myeloid neoplasms, including systemic mastocytosis. The KIT D816V mutation is the most common, leading to constitutive activation of the receptor and its downstream targets, and it is highly resistant to cKIT inhibitors. Metabolic rewiring is a common trait in cancer. We analyzed the metabolic profile induced by the KIT D816 mutation, measuring mitochondrial parameters in two myeloid cell lines. We found that the KIT D816V mutation causes 3 a significant increase in mitochondrial abundance and activity associated with superoxide production, which could promote DNA instability. Functional and morphological changes in mitochondria were associated with reduced levels of BNIP3 protein expression. We also detected low BNIP3 levels in clinical acute myeloid leukemia samples harboring D816V mutations. In addition, we have found a constitutive mTOR activation in mutated cells, a pathway that has been shown to regulate autophagy. Our data suggest that KIT D816V increases mitochondrial activity through BNIP3 down expression, which increases mitochondrial number through the autophagy pathway. Alterations in the cellular metabolism induced by the KIT D816V mutation could be therapeutically exploited.
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CISA-WIECZOREK, Sabina, HERNÁNDEZ-ALVAREZ, María isabel, PARREÑO, Matilde, MUÑOZ, Juan p., BUSSAGLIA, Elena, CARRICONDO, Maite, UBEDA, Jose, DUBREUIL, Patrice, ZORZANO OLARTE, Antonio, BRENET, Fabienne, NOMDEDÉU, Josep. D816V KIT mutation induces mitochondrial morphologic and functional changes through BNIP3 downregulation in human myeloid cell lines ROSA and TF-1. _Experimental Hematology_. 2025. Vol. 143, núm. 1-11. [consulta: 7 de gener de 2026]. ISSN: 0301-472X. [Disponible a: https://hdl.handle.net/2445/219751]